Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Circulating T Cell Polarization Is Associated with Respiratory Decline in Scleroderma Patients with Active Interstitial Lung Disease.
Boin1, Francesco, Wigley2, Fredrick, Wise2, Robert, Rosen2, Antony
Immune activation plays a role in the pathogenesis of systemic sclerosis (SSc) and may be relevant for the initiation and propagation of target tissue injury. In particular, development of interstitial lung disease (ILD) is associated with lung inflammation. The presence of neutrophilia and/or eosinophilia (alveolitis) in the bronchoalveolar lavage (BAL) fluid of SSc patients has been considered indicative of active ILD. However, this measure has not consistently provided reliable prediction of lung disease outcomes. A pro-fibrotic type 2 (Th2/Tc2) T cell response has been detected in the periphery of SSc patients with ILD. In this study we investigated whether an abnormal distribution of polarized T cell subsets in the periphery or the bronchoalveolar lavage (BAL) fluid of SSc patients is associated with the presence of active ILD.
Peripheral blood and BAL were simultaneously obtained from 22 SSc patients undergoing bronchoscopy for suspected active ILD based on increasing respiratory symptoms, worsening lung volumes or abnormal imaging studies. Decline of the forced vital capacity (FVC) >10% of predicted within 610 months prior to the procedure was considered as significant for active ILD. The presence of active BAL alveolitis was defined as neutrophils >3% and/or eosinophils >2.2% on differential cell count. T cell subsets were characterized by flow cytometry using CD3, CD4, CD8, chemokine receptor CCR5 (Th1/Tc1 specific) and CRTH2 (Th2/Tc2 specific) surface markers. CCR5/CRTH2 ratio was used to determine polarization of the immune response towards a type 1 (high ratio) or type 2 (low ratio) phenotype.
Active ILD (FVC decline >10%) was identified in 12 patients and was significantly associated with a relative Th2/Tc2 polarization in the peripheral blood based on a lower CD3+CCR5/CRTH2 ratio (3.9 vs. 11, p<0.001). This finding was mostly determined by a lower number of circulating CCR5+ T cells in active vs. non-active ILD patients (CD3 8.6% vs. 24.8%, p<0.001; CD4 7.7% vs. 19.4%, p=0.005; CD8 14.9% vs. 40%, p<0.001). Conversely, the presence of BAL alveolitis was not significantly associated with declining FVC volumes, nor it was correlated with any absolute or relative difference among polarized T cell subsets in the peripheral blood or BAL fluid.
Distinct polarized T cell subsets in the peripheral blood of SSc patients are associated with declining respiratory function and should be prospectively explored as a novel biomarkers to measure disease activity and predict outcomes in ILD and other clinical manifestations of scleroderma.
To cite this abstract, please use the following information:
Boin, Francesco, Wigley, Fredrick, Wise, Robert, Rosen, Antony; Circulating T Cell Polarization Is Associated with Respiratory Decline in Scleroderma Patients with Active Interstitial Lung Disease. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1989